The broad, long-term objectives of the research program are to define the basic molecular and cellular components required for chemosensory discrimination in Drosophila. This chemosensory model system has many parallels with vertebrate chemosensory systems, but is numerically simpler. The potent molecular genetic tools available in Drosophila combined with simple chemosensory behavior assays will allow us to gain insight into the principles of chemosensory information processing. The specific aims are to: 1. Identify, isolate and determine the biological function of a collection of gene products expressed exclusively in the chemosensory organs, 2. Identify the neuronal transmembrane odorant receptors in Drosophila, and characterize the expression patterns of individual members, and 3. Differentiate between several possible models by which odorant- binding proteins influence chemosensory behavior. Health relatedness: Understanding the molecular basis of chemosensation in Drosophila will provide insights into this process in related arthropods that transmit human diseases. This understanding will faciliate new approaches to control these diseases. The methods for achieving specific aim 1 are to utilize the enhancer trapping approach to identify, isolate, mutate and determine the biological function of a collection of genes we have identified that are expressed exclusively in the chemosensory organs. This method allows us to evaluate the biological function of these chemosensory-specific gene products in intact animals. The methods for achieving specific aim 2 are to use differential hybridization and single chemosensory neuron libraries to identify neuronal chemoreceptors. We will use antibodies to specific receptors and the promoters of receptor genes to drive LacZ reporter genes to map the spatial expression patterns of each gene. Identification of the neuronal receptors that mediate chemosensation is essential to our long-range goal of understanding the molecular basis of chemosensory discrimination. The methods for achieving aim 3 are to mis-express several members of the odorant-binding protein family with known ligand specificity in specific subsets of sensilla to sensitize subsets of chemosensory neurons to specific odorants and determine the resulting behavioral consequences.